Esra YILDIZHAN
Düzce Üniversitesi T›p Fakültesi ‹ç Hastal›klar› Anabilim Dal› DÜZCE
Tlf: 0380 542 14 16 e-posta: esra3yildizhan@hotmail.com Gelifl Tarihi: 24/06/2013 (Received) Kabul Tarihi: 04/12/2013 (Accepted) ‹letiflim (Correspondance)
Düzce Üniversitesi T›p Fakültesi ‹ç Hastal›klar› Esra YILDIZHAN
Yusuf AYDIN Hülya COfiKUN Özlem KUDAfi Elif ÖNDER
THE PREVALENCE AND CHARACTERISTICS OF
ANEMIA IN GERIATRICS IN THE WEST BLACK
SEA REGION, TURKEY
TÜRK‹YE’DE BATI KARADEN‹Z BÖLGES‹NDE
YAfiLILARDA ANEM‹ PREVALANSI VE
ÖZELL‹KLER‹
Ö
ZGirifl: Çal›flman›n amac› pek çok aç›dan özellik gösteren yafll› nüfusta anemi s›kl›¤›n›n ve özel-liklerinin irdelenmesidir.
Gereç ve Yöntem: Bu amaçla Melen çal›flmas› kapsam›nda 2187 kifli incelemeye al›nd›. 65 yafl ve üstü olan 430 kat›l›mc› ‘geriatri grubu’ olarak çal›flman›n odak noktas›n› oluflturdu ve fizik muayene, anamnez ve laboratuar tetkikleri ile anemi s›kl›¤› ve morfolojisi incelendi.
Bulgular: Toplam 430 yafll› kat›l›mc›n›n 138 inde (%32.0) anemi tespit edildi. Kad›nlarda anemi s›kl›¤› %28.0 ve erkeklerde %36.0 bulundu. Anemilerin %40.5’i demir eksikli¤i, %7.9’u kronik hastal›k anemisi, %14.4’ü renal anemi ve %36.9’u aç›klanamayan anemiler olarak de¤er-lendirildi.
Sonuç: Aneminin yafll› kiflilerde genelden farkl› özellikler tafl›d›¤› görülmektedir ve etiyoloji, tedavi ve önlemler aç›s›ndan özel yaklafl›mlar gerektirmektedir. Yapt›¤›m›z çal›flma Türkiye’de yafl-l› hastalarda aneminin tahmin edilenden daha önemli bir sorun olabilece¤ini göstermektedir.
Anahtar Sözcükler: Anemi, Demir Eksikli¤i; Yafll›; Prevalans.
A
BSTRACTIntroduction: The aim of this study was to determine the prevalence and characteristics of anemia in geriatric population, which has important implications.
Materials and Method: As part of the Melen Study 2187 people were examined. All partic-ipants were given a physical examination, medical history and laboratory examinations. Of this larger group, 430 participants aged 65 and above, the “geriatric group”, formed the focus of the present study that evaluated the incidence and morphology of anemia.
Results: Of the 430 geriatrics, 138 (32.0%) were identified as anemic. The prevalence rate of anemia was found to be 28% in women and 36% in men. The etiologies of anemia were found to be iron deficiency anemia, 40.5%; anemia of chronic disease, 7.9%; renal anemia, 14.4%; and unexplained anemia, 36.9%.
Conclusion: We found that anemia has different characteristics in geriatrics that necessitate special approaches in terms of etiology, precautions and treatment. Our study shows that anemia in geriatrics in Turkey may constitute a more important problem than it was thought to be.
Key Words: Anemia, Iron Deficiency; Aged; Prevalence.
A
RAfiTIRMAI
NTRODUCTIONA
nemia is a common problem worldwide; however, it is ofgreat importance in terms of prevention, diagnosis and treatment for special groups such as children, the pregnant and geriatrics.Studies carried out on geriatrics have shown rates of ane-mia ranging between 3 and 61% (1,2). According to the Turkish Statistical Institute database there are 5.7 million people (7.5%) aged over 65 in Turkey and it is estimated that by 2050, 20.8% of Turkish people will be geriatric (3).
The aim of our study was to determine the prevalence and characteristics of anemia in independently living geriatrics and to draw attention to the importance of the matter.
M
ATERIALS ANDM
ETHODStudy Population: The Melen study is a prospectively designed survey aiming to investigate the cardiometabolic risk factors of Turkish people. This study was carried out in May and June 2010, in the citizens of Y›¤›lca town, which is in Düzce, North-east Turkey and has a population of 17,000 people living in the town center and 39 villages. Y›¤›lca town, with an elevation of around 350 metres above sea level, has geological and social characteristics similar to those of West Black Sea region. Two thousand one hundred andeighty-seven adult participiants (1407 women and 780 men), who had been randomized and invited to the health service office, were examined by anamnesis, physical examina-tion and laboratory tests, and were assigned to either the ‘young group’ or the ‘geriatric group’. The geriatric group, consisting of 430 participants (236 women and 194 men) aged 65 and above, formed the main population of study. The study protocol was approved by the Ethics Committee of Duzce University and every subject signed a consent form.
Definitions:Anemia was defined as hemoglobin (Hb) level below 13 g/dl for men and below 12 g/dl for women, in accor-dance with World Health Organization (WHO) criteria (4).
Iron deficiency was defined as ferritin <20 ng/dl or serum iron <40 μg/dl and transferrin saturation (TS) <15%.
Normocytic or microcytic anemia accompanied by iron deficiency was defined as iron deficiency anemia (IDA) (5).
Anemia of chronic disease (ACD) was defined as anemia that does not meet the criteria for iron deficiency and that has serum iron <60 μg/dl and glomerular filtration rate (GFR) >30 ml/dk, along with diagnosed chronic inflammatory dis-ease or elevated inflammatory markers (ferritin>100 ng/dl or high-sensitivity C- reactive protein (hsC-RP) >4mg/dl).
The Cockcroft-Gault Formula (6) was used to calculate GFR, and renal anemia was defined as anemia in which GFR<30 ml/min/1.73m2 or normocytic and microcytic
ane-mias that do not meet the criteria for IDA and ACD when GFR is between 60-30 ml/min/1.73m2.
The reference intervals were set at 80 to 95 fl for mean corpuscular volume (MCV), 0.4 to 4 IU/ml for thyrotropin and 0.8 to 1.7 μg/dl for free thyroxine.
The cut-off levels were 200 pg/ml for vitamin B12
(cobal-amin) and 2 ng/ml for folate. A combination of cobalamin and folate deficiency along with MCV>95 fl was defined as mega-loblastic anemia.
Those conditions that could not be identified by the cri-teria mentioned above were considered as ‘unexplained ane-mia’.
Monthly or less frequent meat consumption was consid-ered as inadequate meat consumption.
Biochemical and Complete Blood Count Analysis:Ten mil-liliters of blood was drawn from the antecubital vein by applying minimal tourniquet force. 2 ml of blood was drawn into vacutainer tube containing 7.5% K3 salt of ethylenedi-aminetetraacetate (EDTA) and 8 ml of blood was drawn into a vacutainer tube without anticoagulant. Blood samples were allowed to clot for 20 minutes and then centrifuged for 10 min at 1500 x g. Sera were shipped within a few hours on cooled gel packs at 2-50C to Duzce University’s central
labo-ratory and kept in Eppendorf tubes frozen at ?80 °C until final analyses.
Complete blood counts were done using CELL-DYN 3700 SL analyzer (Abbott Diagnostics, Chicago, USA). Serum iron, total iron binding capacity (TIBC) and ferritin levels were measured with commercial kits using cobas 6000 auto analyzer (Roche Diagnostics GmbH, Mannheim, Germany). Serum cobalamin and folate levels were measured by the Siemens IMMULITE 2000 competitive chemiluminescent enzyme immunoassay method (CCEA).
Statistical Analyses: Statistical Package for the Social Sciences software (SPSS 12, Chicago, IL, USA) was used for analysis. Descriptive parameters were shown as mean ± stan-dard deviation or in percentages. Two-tailed t-tests and Pearson’s chi-square tests were used to analyze the differences in means and proportions between groups. Non-normally dis-tributed variables were compared using Mann-Whitney U tests. A p value of <0.05 was considered significant.
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ESULTSA
nemia was diagnosed in 32% (n=138) of the geriatricgroup, compared to 24% rate of anemia in the young group (p=0.001). The average age of the geriatric group was 71±5 and 28% of women and 36% of men were identified as anemic in this group (p=0.07). In terms of such social factors as chronic diseases, diet and level of income, the young group and the geriatric group were significantly different (Table 1). In the geriatric group, mean Hb concentration was 12.5±1.3g/dl for women and 13.4±1.3 g/dl for men. Mean Hb concentration in the geriatric group was lower than in the young group (respectively 12.9±1.4 vs 13.1±1.6 g/dl, p=0.006). Although mean cobalamin level was higher in the geriatric group (young group 266±126 vs geriatric group 307.4±166 pg/ml; p<0.001), cobalamin deficiency was more frequent (Table 1).Ninety seven (22%) geriatrics (58 female, 39 male) had iron deficiency; the difference, in terms of gender, was non-sig-nificant (60% women and 40% men, p=0.28). One hundred and six (24%) geriatrics, 51(48%) women and 55 (52%) men, had cobalamin deficiency (p=0.045). Folate deficiency was detected in 30 geriatrics (6%) (Figure 1). Despite the high fre-quency of deficiences, megaloblastic anemia was not detected.
There was no history of malignancy, chemotherapy, con-nective tissue diseases, inflammatory bowel diseases and gas-trointestinal hemorrhage in the last 6 months in the anemic participants. There was no history of drug use that could have been responsible for anemia.
MCV values were within normal limits in 94 (68%), low in 43 (31%), and high in only one of the total 138 anemic geriatrics (p<0.001). There was no significant association between cobalamin or folate deficiency and MCV.
Table 1— Characteristics and Laboratory Parameters of Study Population.
Geriatric Group (n=430) Young Group (n=1757) p Mean±sd or n (%) Age (year) 71.71±5.61 44.64±11.81 <0.001 Gender (women) 236 (54%) 1171 (66%) 0.001 Anemic 138 (32%) 427 (24%) 0.001 CKD 5 (1.2%) 7 (0.3%) 0.006 COPD 62 (14%) 97 (5%) <0.001 Chronic medication 283 (65%) 683 (38%) 0.001
Adequate meat consumption 286 (66%) 1607 (91%) 0.001
Income level (YTL) 587.71±381.52 846.39±672.44 <0.001
Hemoglobin (12-18 g/dl) 12.9±1.4 13.1±1.6 0.006 MCV (80-95 fl) 84.1±6.8 82.7±6.6 <0.001 Iron (37 – 145 μg/dl) 79.48±32.93 80.61±36.04 0.56 Ferritin (15-150 ng/dl) 198.97±387.01 192.21±164.40 0.58 TS (15-50%) 22.64±9.75 22.10±10.6 0.33 TIBC (300-360 μg /dl) 361.22±67.69 379±68.57 <0.001 Cobalamin (191-663 pg/ml) 307.47±166.88 266.16±126.69 <0.001 Folate (4.6-18.7 ng/ml) 8.73±4.15 8.59±3.86 0.51
CKD: chronic kidney disease COPD: chronic obstructive pulmonary disease MCV: mean corpuscular volume RDW: red blood cell distribution width TS: transferrin satura-tion TIBC: total iron binding capacity.
Figure 1— Distribution of anemia, iron, cobalamin, folate and gender
When the geriatrics with and without iron defficiency were compared, there were no significant differences in terms of gender, cobalamin, or folate levels, and also social factors such as level of income, living in a rural area and meat con-sumption (p>0.1). Unlike the other iron parameters, there was no significant difference between the means of ferritin levels between the two groups (191.1±176 vs 201.3±431 ng/dl; p=0.3) (Table 2).
When the geriatrics were grouped according to their cobalamin levels, the participants with low and normal cobal-amin levels were similar in terms of Hb concentration, MCV, anemia frequency and meat consumption (p>0.5) (Table 2).
Three anemic geriatrics were identified with manifest hypothyroidism (free thyroxine<0.8 μg/dl). Two of them were identified as IDA and one as ACD. Anemia resulting mainly from hypothyroidism was not identified.
For the geriatrics with and without anemia, comparisons with respect to cobalamin and folat deficiency, hypothy-roidism, the presence of type 2 diabetes, hypertension, chron-ic obstructive pulmonary disease (COPD) and hsC-RP level were not significant (Table 3).
The Hb concentration was over 10 g/dl in 92% and below 8 g/dl in 4% of anemic geratrics.
When the anemias were classified according to the domi-nant etiology, IDA was identified as the most common one (40.5%). The rate of renal anemia was identified as 14.4%, ACD as 7.9% and unexplained anemia as 36.9% (Figure 2).
Forty (78.4%) of the geriatrics with unexplained anemia had normocytic red cells and 11 (21.6%) had microcytic red cells. Macrocytic anemia was not identified in this group. Of the geriatrics with unexplained anemia, 5 had COPD, 2 had subclinic hypothyroidism (one had thyrotropin >10 IU/mL), and 1 reported alcohol consumption; these were factors that could be associated with anemia. Although they did not meet the criteria for ACD (since their serum iron levels were >60 μg/dl), in 9 geriatrics with unexplained anemia the hsC-RP levels were >4 mg/dl, (4 of them >10 mg/dl), and in 12, fer-ritin levels were >300 ng/dl. There was renal insufficiency (GFR<60 ml/dk) along with iron deficiency in 15, presence of inflammation markers (TS>15%, serum iron<60 μg/dl, and ferritin>100 ng/dl and/or hsC-RP>4 mg/dl) along with iron defficiency in 6, and renal insufficiency along with pres-ence of inflammation markers in 3 of the anemic geriatrics. In 21% of all anemic geriatrics and 30% of anemic geriatrics with known etiology, there were multiple factors responsible for etiology. The anemia in 51 geriatrics, whose anemia etiol-ogy was not clearly identified, was considered to be unex-plained anemia.
D
ISCUSSIOND
espite various studies on the prevalence and characteric-tics of anemia in geriatrics, it is difficult to compare their results since these studies contain differences in the definitionTable 2— Comparison of Geriatrics in Terms of Iron and Cobalamin Deficiency.
With Iron Without Iron With Cobalamin Without Cobalamin Deficiency Deficiency Deficiency Deficiency
(n=97) (n=33) p (n=106) (n=324) p Mean±sd or n (%) Age; year 71.8±5.9 71.62±5.54 0.68 71.81±5.28 7.65±5.80 0.81 Gender; women 58 (60%) 177 (53%) 0.28 51 (48%) 141 (43%) 0.045 Hemoglobin gr/dl 12.0±1.6 13.18±1.22 <0.001 12.93±1.59 12.94±1.32 0.96 MCV fl 81.0±6.5 85.22±4.79 <0.001 84.32±6.17 84.32±4.91 0.94 TS % 11.5±3.9 26.03±8.39 <0.001 Demir μg/dl 46.4±17.7 89.4±29.76 <0.001 Ferritin ng/dl 191±176 201±413.13 0.83 Anemic 56 (57%) 82 (24%) <0.001 37 (34%) 75 (23%) 0.56 Folate deficiency 6 (6.2%) 24 (7.5%) 0.67 7 (0.6%) 15 (0.4%) 0.94 Cobalamin deficiency 24 (25.0%) 80 (25.2%) 0.90 Iron deficiency 24 (22%) 53 (16%) 0.9
of anemia and in the characteristics of study populations. The rate of anemia (32%) was higher in our study than in similar studies. In NHANES III, an important study on this subject,
the rate of anemia was 10.2% for elderly women and 11% for men (7). In 2000, Olivares et al. (8) from Chile found the rate of anemia to be 4.4% for women and 5.4% for men. Tettamanti et al. (9) in Italy found the rate of anemia to be 14%. In the Framingham heart study (10), 6.1% of men and 10.5% of women were reported to be anemic. In these stud-ies, WHO criteria were used in the assessment of anemia and apparently healthy geriatrics living independently were stud-ied.
Few studies have been conducted in Turkey on the anemia in geriatric population. Çoban et al. (11) from Antalya report-ed the rate of anemia to be 30% in 2100 geriatrics. In anoth-er study from Adana carried out on 501 ganoth-eriatrics, Erkan et al. (12) reported the rate of anemia to be 32.5%. Both of these studies were carried out on patients aged 65 and over who had been referred to the internal medicine outpatient clinic so, it can be inferred that they had high rates of comorbidities and chronic diseases. Our study was carried out with ‘community dwelling apparently healthy’ geriatrics. There was no history of malignancies or chronic inflammatory diseases, except for COPD, among our participants. When these factors that
Table 3— Comparison of Geriatrics With and Without Anemia.
Anemic (n=138) Not Anemic (n=292) p Mean or n (%) Gender, women 67 (48.5%) 169 (57.8%) 0.07 Age 72.8 71.1 0.004 Hemoglobin g/dl women 10.9 13.1 <0.001 men 12.0 14.2 Iron μg/dl 67 85 <0.001 Ferritin ng/dl 183 206 0.5 Transferrin saturation % 18 24 <0.001 TIBC mcg/dl 373 355 0.01 Folate ng/ml 8.8 8.6 0.6 Cobalamin pg/ml 315 303 0.5 Income YTL 566 597 0.4
Diyabetes Mellitus and/or Hypertension 68 (49.2%) 160 (54.7%) 0.55
COPD (diagnosed) 21 (15.2%) 41 (14%) 0.7 CKD (diagnosed) 1 (0.7%) 4 (1.3%) 0.18 GFR<60 ml/dk 40 (28%) 45 (15.4%) 0.008 Iron deficiency 56 (40.5%) 41 (14%) <0.001 Folate deficiency 10 (7.6%) 20 (6.8%) 0.84 Cobalamin deficiency 37 (26.8%) 69 (23.6%) 0.56 Manifest hypothyroidism (fT4<0.8 μg/dl) 3 (2.1%) 10 (3.4%) 0.49
Alcohol consumption (>20 gr daily) 4 (2.8%) 2 (0.6%) 0.07
TS: transferrin saturation TIBC: total iron binding capacity hsC-RP: high sensitive C-reactive protein COPD: chronic obstructive pulmonary disease CKD: chronic kidney dis-ease GFR: glomerular filtration rate.
accompany aging were excluded, this high rate of anemia underlies the importance of studies in which anemia criteria and cut off levels have been questioned in special groups such as geriatrics (13,14).
Our study indicated that in geriatrics, cobalamin and folate deficiency were frequent and to identify the mega-loblastic anemia we used increased MCV. However, especial-ly in geriatrics, since mixed nutritional deficiencies and fac-tors causing microcytic anemia often accompany cobalamin and folate deficiency, there might be patients who went unno-ticed. In almost one out of every four patients, cobalamin was low and in 25% of cases there was iron deficiency along with cobalamin deficiency. Besides, anemia due to cobalamin or folate deficiency was not identified in geriatrics. As it has also been shown in the Leiden 85-Plus study, association of cobal-amin or folate deficiency with anemia was poor, only severe deficiencies were related to anemia (15).
In the NHANES III study 34% of anemias were nutri-tional and the proportion of IDA was 20% in nutrinutri-tional ane-mias (7). In our study there was iron deficiency in 22% of all geriatrics and IDA was the most common type of anemia, with a rate of 41%. Although in most anemics with iron defi-ciency the red cells were microcytic, almost one in five was normocytic. Mixed anemia that includes hypothyroidism and cobalamin deficiency, which is frequent in our population, may be the reason for that result. When patients are assessed in terms of iron deficiency, measuring ferritin levels to evalu-ate body iron store is a common approach. However, ferritin physiologically rises with age and there is a high occurance of inflammatory diseases in geriatrics (5,16). So, ferritin loses its importance in the diagnosis of IDA in this population, partic-ularly for the values above 15 ng/dl. In fact, we found that the ferritin levels were similar in geriatric groups with and with-out iron deficiency.
In our study we found unexplained anemia to be 37%; although we did not use advanced examinations, this rate is much higher than expected for community dwelling people. In fact, the ‘unexplained anemia’ statement is not appropriate for this group. When advanced examinations are conducted, the potential factors responsible for anemia can be identified, and the truly unexplained, or senile or idiopathic anemias can be detected. For instance, although we did not note renin-angiotensin system inhibitors (RAS-I) as a drug which leads to anemia, 15 of geriatrics with unexplained anemia had been using RAS-I. Some studies have reported that RAS-I may lead to anemia via erythropoietin (17,18). Likewise, COPD may lead to anemia because it is an inflammatory disease (19).
When other reasons are excluded with advanced examina-tions, this knowledge can be significant in determining unex-plained anemias. Nevertheless, even in some studies carried out using advanced examinations such as bone morrow aspi-ration and hemoglobin electrophoresis, unexplained anemia was still high. For instance, in a recent study by Artz and Thirman (20) in 2011, 170 anemic geriatrics from hematol-ogy clinic were assessed and it was found that 43.7 % of ane-mias were unexplained aneane-mias. In 2011 Price et al. (21) studied the etiology of anemia in geriatrics using advanced examinations; however, they could not identify 35% of the etiologies.
When trying to classify the anemias in terms of etiology, it must not be forgotten that plenty of cases are multifactori-al. Fifteen of 56 geriatrics whom we considered IDA experi-enced at least stage-3 renal insufficiency, six of them had COPD associated with inflammation and two of them had manifest hypothyrodism (fT4<0.8 μg/dl). Since chronic inflammation and impaired iron absorbtion have a significant role in the pathogenesis of anemias associated with CKD, it is not possible to make clear distinctions between renal anemia and ACD. Therefore, the term ‘dominant etiology’ is more convenient for these conditions.
Limitations of the Study
The Melen study, whose data we used, was conducted to eval-uate cardioprotective effects. For that reason, parameters such as peripheral blood smear, reticulocyte index, transferrin receptor index, homocysteine and bone morrow aspiration could not be examined. Therefore, it was not possible to dis-tinguish the real idiopathic anemias.
In conclusion, this cross-sectional study demonstrates that anemia in the Turkish geriatric population may constitute a more frequent and major problem than expected. There have been very few studies on this issue in Turkey, and the present study is one of the significant ones conducted with communi-ty dwelling geriatrics. Finally, we would like to emphasise that anemia should not be considered as an outcome of age-ing.
We would like to declare that there is not conflict of interest.
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